Osteoarthritis is a condition that affects many millions of persons in the world for which to date there has been no effective treatment to resolve the complaint definitively and directly on the chondral lesion.
This disease consists of the gradual degeneration and destruction of the articular cartilage due to traumas and structural deformities of the joints and overweight. This process thins the cartilage through a phenomenon called apoptosis, or programmed cell death. When the surface area has disappeared due to the thinning, there is a grade I osteoarthritis; when the tangential surface area has disappeared, there is a grade two osteoarthritis. There are other levels of degeneration and destruction, which affect the deep and the calcified layers that border with the subchondral bone.
The clinical manifestations of the development of the condition are: increased volume of the joint, pain, crepitation and functional disability that, gradually and steadily, first hinders the performance of lengthy walks and forced flexion and extension movements, depending on the affected joint, and then pain and limitation of minimum efforts emerge as well as pain at rest which interrupts sleeping. If the condition persists without correction and/or therapy, the joint is totally destroyed, leading the patient to major replacement surgery with total prosthesis, or to disability.
Therapeutic methods for the correction of the articular cartilage lesions that appear during the osteoarthritic disease have been developed, but so far none of them have been able to achieve the regeneration of articular cartilage in situ and in vivo.
Among the methods we find the following:                a) The application of tendinous, periosteal, fascial, muscular or perichondral grafts.        b) The implantation of fibrin or cultured chondrocytes. (Osteochondral Grafts Improve Symptoms but May Increase Risks Of Osteoarthritis. medscape.com/con/2000/AAOS/story.cfm).        c) The administration of chondrogenic stimulating factors such as “insulin-like growth factors I and TGF-B”.        d) Implantation of synthetic matrices, such as collagen, carbon fiber.        e) Others, such as electromagnetic fields. (J. Buckwalter, M. D., Van C. Mow, Ph. D. and Anthony Ratcliffe, Ph.D. Journal of the American Academy of Orthopaedic Surgery 1994; 2:192-202).All of these have reported minimal and incomplete results with formation of repair, but not regenerative tissue, resulting in a poor quality tissue that can neither support the weighted load nor allow the restoration of an articular function with normal movement.        
The treatment that has 74% to 90% effectiveness and produces excellent results, similar to that presented in this invention, is the transplantation of cultured autologous chondrocytes, a treatment started in 1987 in Sweden and in 1995 in the USA. It consists of taking chondral cellular material from the patient, sending it to a laboratory where it is seeded in a proper medium for its proliferation, and, once enough volume is achieved after a variable period that may last from weeks to months, transporting it in a special container and implanting it in the damaged tissues to cover the tissue's defects. This is an expensive procedure that requires the patient to be in the operating room for the removal of the necessary cellular material, and subsequently for the implantation of the proliferated material. Furthermore, a waiting period is needed for the implant to be ready. (VLADIMIR, Bobic, MD AAOS Annual Meeting, Mar. 16, 2000.)
A recent treatment, currently in vogue, is the intraarticular instillation of Hylan G-F 20 (Synvisc, Hyalgan, Artz etc.), a modified form of one of the substances contained in the product used in this invention. This substance only acts on the rheologism of the synovial fluid, producing an almost immediate sensation of free movement and a marked reduction of pain: however, its effect is temporary because that element remains within the articular chamber for only 72 hours before it is absorbed and metabolized. The residual effects of this substance act on the synovial receptors causing a pain reduction that lasts several weeks and even months. However, this isolated effect is counterproductive for the course of the disease and for the viability of the cartilage because, as it masks the symptoms, the joint is used with more intensity and its destruction is accelerated as the original problem is not corrected and the the damaged articular cartilage is not restored.
As an antecedent to this invention, in 1982, the applicant began applying sodium hyaluronate (SH) to thoroughbred race horses in his stable at Hipódromo de las Américas (Las Américas Race Track), in Mexico City, because the knees and ankles are the most commonly injured joints in these horses. Veterinarians at racetracks in the USA had already used this procedure, observing the beneficial reaction that this compound produced in the injured knees of the horses. The applicant considered its use in humans, with the addition of some substance to cause the restoration of the damaged surface.
The applicant observed that chondroitin sulfate (Cs), the most important part of the Agreecan molecule, lengthy chains bound to the core-protein, which are the basis of chondral support, might have a repaving effect.
In 1996 while visiting Alcon Laboratories in Mexico City, the applicant found out that one of the company's ophthalmologic products contained both above mentioned substances in a gel suspension (VISCOAT). The inventor obtained detailed information, including the product monograph that states that it has no reported side effects in intraocular use; furthermore, there are ample references from efficacy and safety studies of this product (CILCO, In, Summary of safety and efficacy for Viscoat, 1984). It was then that the applicant decided to use it in patients with osteoarthritis disorders of all degrees, and subsequently perform an analysis.
The above mentioned usual treatments include antiinflammtatories, antirheumatics, systemics, physiotherapy, infiltration of depot steroids and, recently, viscoprotection has emerged. It includes substances such as high molecular weight hyaluronic acid (Hylan G F 20) which is instilled in the joint and reduces the painful symptoms.
It has been proven that the change of the intraarticular fluids produces a blockage of the nociceptors of subsynovial and capsular tissues and that, in addition to the mechanical factors of the osteochondral pathology, the fluids exert a relevant influence with their lubricating properties. Thus the change in viscosity of these fluids acts favorably on the painful osteochondral symptoms when sodium hyaluronate is instilled.
Recent studies of a 5 year follow-up with these substances indicate that the clinical improvement is important and that it represents a remission factor of painful symptoms at short and medium term. However, adverse effects, characterized by severe pain, important synovial effusion, rash and ankle edema, have been reported in at least 7.2% of the treated patients.
This study reveals another alternative in the management of osteochondral lesions of the knee through the intraarticular application of the mixture of sodium hyaluronate and sodium chondroitin sulfate, based on the principles of chondrogenesis and viscoelasticity by implanting an artificial matrix that represents an indispensable repair factor, as in it the cloned chondrocytes can proliferate and restore the solution of continuity, regenerating the destroyed cartilage with the same original characteristics.
With this matrix, the symptomatic evolution is significantly favorable and long lasting due to the regeneration of chondral lesions and no side effects have been reported except in a patient who reported pain and a slight increase in Volume at the site of application, which subsided spontaneously in 24 hours; he was only given acetaminophen as an analgesic.
It must be pointed out that the product is applied exactly as it is presented for intraocular use and no change has been made in the formulation. A change in presentation with a larger capacity syringe is now being proposed, as the current presentation has 0.5 c.c. and 0.75 c.c. syringes.
It must also be pointed out that although this is the same preparation as that used intraocularly, its use for this purpose is totally different as it is applied in a conventional intraarticular manner as an inductor of chondrogenesis, to regenerate the cartilage destroyed by osteoarthritis.
As previously mentioned, experimental application of the compound in humans started in 1996, and excellent results noted. These were confirmed later by arthroscopy studies (direct view of the articular cartilage through the insertion of a camera into the joint), pathologic anatomy and histophysiologic studies, all of them consistent with the clinical findings that the regeneration of normal articular cartilage was achieved. This is why this treatment is presented as the only currently available procedure that can offer up to 95% regeneration of articular cartilage damaged by grade I and II osteoarthritis in any joint of the human body.